Title:GRβ Regulates Glucocorticoid Resistance in Sudden Sensorineural Hearing Loss
Volume: 22
Issue: 9
Author(s): Xubo Chen, Qi Zhang, Chunping Yang, Yuehui Liu and Lihua Li*
Affiliation:
- Department of Otolaryngology, Head and Neck Surgery, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006,China
Keywords:
Glucocorticoid resistance, dexamethasone, sudden sensorineural hearing loss, GRβ, SRp30c, LPS.
Abstract:
Background: In recent years, the incidence of sudden deafness has gradually increased,
with a very limited understanding of its etiology and pathogenesis. Glucocorticoids are the first choice
of the treatment, but some hormone-resistant patients are not sensitive to glucocorticoid therapy. The
pathogenesis is not yet known. In this study, we aim to construct the HEI-OC1 cell line stably overexpressing
Glucocorticoid Receptor Beta (GRβ), and identify its exact role in the cases of glucocorticoidresistant
sudden deafness.
Methods: We used the endotoxin lipopolysaccharide-stimulated cochlear hair cells (HEI-OC1) to investigate
the relationship of inflammation factor IL-2, TNF alpha, and SRp30c with the high expression
GRβ. We built a stable GRβ high expression HEI-OC1 cell line and clarified its effects on the
therapeutic effect of dexamethasone. MTT assay, colony formation assay, CCK-8 assay, Western blot,
and RT-qPCR were utilized for characterizations.
Results: Dexamethasone reduced the LPS-induced inflammatory response from HEI-OC1 cells (p<0.05),
detected by MTT assay. Dexamethasone could protect HEI-OC1 cells, but its protective effect was weakened
due to the transfection of SRp30c over-expression plasmid (p<0.05). The transfection of SRp30c
over-expression plasmid in HEI-OC1 cells could elevate the expressions of GRβ (p<0.05).
Conclusion: We clarified the mechanisms of high expression of GRβ in glucocorticoid-resistant sudden
sensorineural hearing loss, and proved that the inhibition of SRp30c may act as a new treatment
way of glucocorticoid-resistant sudden sensorineural hearing loss.